Research: Sensing oxygen

4 January 2006

New research has found that an ion channel's sensitivity to oxygen deprivation depends on how its RNA is processed.

Mammalian cells depend on oxygen for their survival and must respond quickly if levels drop (hypoxia). This response is mediated, in part, by particular potassium channels known as BK channels (short for large-conductance voltage- and calcium-activated potassium channels). Why some of these channels are exquisitely sensitive to hypoxia, while others are almost insensitive, has now been uncovered by a team led by Dr Iain Rowe and Dr Mike Shipston at the University of Edinburgh, with collaborators at the University of Strathclyde.

The channel's pore is built from four subunits coded for by KCNMA1, a gene that undergoes extensive pre-mRNA splicing. The new research found that the channels were only sensitive to hypoxia when a particular splice variant, containing the stress-regulated exon (STREX), was expressed.

This exon encodes a motif, highly conserved throughout evolution, that when mutated leads to the abolition of hypoxia-sensitivity. As the expression of the STREX variant is tissue-specific, and can be regulated dynamically, it may be that alternative splicing of BK channels allows for differing sensitivity of tissues to hypoxia to be established, and to be altered according to the body's needs.

External links

• McCartney CE et al. A cysteine-rich motif confers hypoxia sensitivity to mammalian large conductance voltage- and Ca-activated K (BK) channel alpha-subunits. Proc Natl Acad Sci USA 2005;102(49):17870–6.